Project Summary Bacteria colonize surfaces, including the tissues of the human body, as complex and structured communities called biofilms. As a result, bacterial biofilms influence human health. Some biofilms are pathogenic, and because the bacteria in biofilms can be phenotypically and metabolically distinct from their planktonic, free-swimming cousins, they can be difficult to control or eradicate using conventional means. As a result, persistent chronic infection from biofilms represents a serious problem that characterizes about two-thirds of infections treated by physicians in the developed world (Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: A common cause of persistent infections. Science. 1999;284:1318?1322). The bacterial predator Bdellovibrio bacteriovorus has been shown to consume bacterial biofilms robustly, and thus holds promise as a potential biofilm control agent. However, it is critical to understand at the molecular level how the predator differentiates between prey and non-prey cells. Since B. bacteriovorus is harmless to eukaryotes and is member of the human microbiome, both the specific and general biochemical knowledge produced by these experiments may lead to new, innovative means to control Gram-negative bacterial biofilms. The proposed experiments use model organisms that are nonpathogenic but that have close relatives that cause human pathogenicity. Moreover, given that no conferred genetic resistance to B. bacteriovorus has been found in the 53 years since the first published paper on this bacterial predator, drug- resistant and pathogenic strains affecting human health (e.g., contaminated joint implants, biofilms in the lungs of cystic fibrosis patients, skin infections) are among the most relevant applications of the proposed research findings.